SummaryRNA viruses have extreme mutation frequencies. When a RNA virus replicates, nucleotide mutations are generated resulting in a population of variants. This genetic diversity creates a cloud of mutations that are potentially beneficial to viral survival, but the majority of mutations are detrimental to the virus. By increasing the mutation rate of a RNA virus, viral fitness is reduced because it generates more errors, and attenuates the virus during in vivo infection. Another feature that affects RNA virus fitness is mutational robustness. Mutational robustness is the ability to buffer the negative effects of mutation.
The attenuation of RNA viruses for vaccine production faces problems of genetic instability and reversion to a pathogenic phenotype. The conventional method for attenuation is mostly empirical and specific to the particular RNA virus species. Hence, it cannot be universally applied to a variety of virus types. We've developed a non-empirical, rational means of attenuating RNA viruses, targeting mutational robustness as modifiable trait. We demonstrate that mutational robustness of RNA viruses can be modified without changing a virus' physical and biological properties for vaccine production; yet the virus is attenuated as it becomes victim of its naturally high mutation rate. Specifically, the genome of RNA viruses are modified so that a larger proportion of mutations become lethal Stop mutations. Our technology places the virus one step away from these Stop mutations (1-to-Stop). We succeeded in attenuating two RNA viruses from very different viral families, confirming the broad applicability of this approach. These viruses were attenuated in vivo, generated high levels of neutralizing antibody and protected mice from lethal challenge infection.
The proposal now seeks to complete proof of concept studies and develop commercialization strategies to scale up this new technology to preclinical testing with industrial partners.

RNA viruses have extreme mutation frequencies. When a RNA virus replicates, nucleotide mutations are generated resulting in a population of variants. This genetic diversity creates a cloud of mutations that are potentially beneficial to viral survival, but the majority of mutations are detrimental to the virus. By increasing the mutation rate of a RNA virus, viral fitness is reduced because it generates more errors, and attenuates the virus during in vivo infection. Another feature that affects RNA virus fitness is mutational robustness. Mutational robustness is the ability to buffer the negative effects of mutation.
The attenuation of RNA viruses for vaccine production faces problems of genetic instability and reversion to a pathogenic phenotype. The conventional method for attenuation is mostly empirical and specific to the particular RNA virus species. Hence, it cannot be universally applied to a variety of virus types. We've developed a non-empirical, rational means of attenuating RNA viruses, targeting mutational robustness as modifiable trait. We demonstrate that mutational robustness of RNA viruses can be modified without changing a virus' physical and biological properties for vaccine production; yet the virus is attenuated as it becomes victim of its naturally high mutation rate. Specifically, the genome of RNA viruses are modified so that a larger proportion of mutations become lethal Stop mutations. Our technology places the virus one step away from these Stop mutations (1-to-Stop). We succeeded in attenuating two RNA viruses from very different viral families, confirming the broad applicability of this approach. These viruses were attenuated in vivo, generated high levels of neutralizing antibody and protected mice from lethal challenge infection.
The proposal now seeks to complete proof of concept studies and develop commercialization strategies to scale up this new technology to preclinical testing with industrial partners.

Max ERC Funding

150 000 €

Duration

Start date: 2016-09-01, End date: 2018-02-28

Project acronymAB-SWITCH

ProjectEvaluation of commercial potential of a low-cost kit based on DNA-nanoswitches for the single-step measurement of diagnostic antibodies

Researcher (PI)Francesco RICCI

Host Institution (HI)UNIVERSITA DEGLI STUDI DI ROMA TORVERGATA

Call DetailsProof of Concept (PoC), ERC-2016-PoC, ERC-2016-PoC

Summary"Antibodies are among the most widely monitored class of diagnostic biomarkers. Immunoassays market now covers about 1/3 of the global market of in-vitro diagnostics (about $50 billion). However, current methods for the detection of diagnostic antibodies are either qualitative or require cumbersome, resource-intensive laboratory procedures that need hours to provide clinicians with diagnostic information. A new method for fast and low-cost detection of antibodies will have a strong economic impact in the market of in-vitro diagnostics and Immunoassays.
During our ERC Starting Grant project ""Nature Nanodevices"" we have developed a novel diagnostic technology for the detection of clinically relevant antibodies in serum and other body fluids. The platform (here named Ab-switch) supports the fluorescent detection of diagnostic antibodies (for example, HIV diagnostic antibodies) in a rapid (<3 minutes), single-step and low-cost fashion.
The goal of this Proof of Concept project is to bring our promising platform to the proof of diagnostic market and exploit its innovative features for commercial purposes. We will focus our initial efforts in the development of rapid kits for the detection of antibodies diagnostic of HIV. We will 1) Fully characterize the Ab-switch product in terms of analytical performances (i.e. sensitivity, specificity, stability etc.) with direct comparison with other commercial kits; 2) Prepare a Manufacturing Plan for producing/testing the Ab-switch; 3) Establish an IP strategy for patent filing and maintenance; 4) Determine a business and commercialization planning."

"Antibodies are among the most widely monitored class of diagnostic biomarkers. Immunoassays market now covers about 1/3 of the global market of in-vitro diagnostics (about $50 billion). However, current methods for the detection of diagnostic antibodies are either qualitative or require cumbersome, resource-intensive laboratory procedures that need hours to provide clinicians with diagnostic information. A new method for fast and low-cost detection of antibodies will have a strong economic impact in the market of in-vitro diagnostics and Immunoassays.
During our ERC Starting Grant project ""Nature Nanodevices"" we have developed a novel diagnostic technology for the detection of clinically relevant antibodies in serum and other body fluids. The platform (here named Ab-switch) supports the fluorescent detection of diagnostic antibodies (for example, HIV diagnostic antibodies) in a rapid (<3 minutes), single-step and low-cost fashion.
The goal of this Proof of Concept project is to bring our promising platform to the proof of diagnostic market and exploit its innovative features for commercial purposes. We will focus our initial efforts in the development of rapid kits for the detection of antibodies diagnostic of HIV. We will 1) Fully characterize the Ab-switch product in terms of analytical performances (i.e. sensitivity, specificity, stability etc.) with direct comparison with other commercial kits; 2) Prepare a Manufacturing Plan for producing/testing the Ab-switch; 3) Establish an IP strategy for patent filing and maintenance; 4) Determine a business and commercialization planning."

Max ERC Funding

150 000 €

Duration

Start date: 2017-02-01, End date: 2018-07-31

Project acronymANTS

ProjectA new technology of microthermal sensing for application in microcalorimetry

Researcher (PI)Rivadulla Fernandez Jose Francisco

Host Institution (HI)UNIVERSIDAD DE SANTIAGO DE COMPOSTELA

Call DetailsProof of Concept (PoC), ERC-2016-PoC, ERC-2016-PoC

SummaryANTS aims to prove the viability of a novel thermal microsensor, with highly improved thermal, temporal and spatial resolution, to be the basis of a breakthrough micro/nano-calorimeter. The resulting device shall quantify binding rates and enthalpy/entropy changes in interactions of biological interest in a much more accurate and straightforward manner than available techniques. Consequently, ANTS-microcalorimeter will facilitate enormously drug discovery and development of biomedical products and technologies. We propose to exploit the large Nernst effect in ferromagnetic conductors for electrical sensing of temperature gradients with exceptional sensitivity. The active sensing elements are composed of a single material, thus offering important advantages for miniaturization over conventional micro-calorimetry, based on diverse Peltier modules, whereas easy to fabricate by standard, scalable deposition and photolithographic methods. Standard microcalorimeter configuration can also be maintained in the novel device, which is convenient to ensure compatibility and foster adoption by users and manufacturers.

ANTS aims to prove the viability of a novel thermal microsensor, with highly improved thermal, temporal and spatial resolution, to be the basis of a breakthrough micro/nano-calorimeter. The resulting device shall quantify binding rates and enthalpy/entropy changes in interactions of biological interest in a much more accurate and straightforward manner than available techniques. Consequently, ANTS-microcalorimeter will facilitate enormously drug discovery and development of biomedical products and technologies. We propose to exploit the large Nernst effect in ferromagnetic conductors for electrical sensing of temperature gradients with exceptional sensitivity. The active sensing elements are composed of a single material, thus offering important advantages for miniaturization over conventional micro-calorimetry, based on diverse Peltier modules, whereas easy to fabricate by standard, scalable deposition and photolithographic methods. Standard microcalorimeter configuration can also be maintained in the novel device, which is convenient to ensure compatibility and foster adoption by users and manufacturers.

SummaryThe ERC starting grant GECOMETHODS, on which this POC is based, tackled problems of diffusion equations via geometric control methods. One of the most striking achievements of the project has been the development of an algorithm of image reconstruction based mainly on non-isotropic diffusion. This algorithm is bio-mimetic in the sense that it replicates the way in which the primary visual cortex V1 of mammals processes the signals arriving from the eyes. It has performances that are at the state of the art in image processing. These results together with others obtained in the ERC project show that image processing algorithms based on the functional architecture of V1 can go very far. However, the exceptional performances of the primary visual cortex V1 rely not only on the particular algorithm used, but also on the fact that such algorithm “runs” on a dedicated hardware having the following features: 1. an exceptional level of parallelism; 2. connections that are well adapted to transmit information in a non-isotropic way as it is required by the algorithms of image reconstruction and recognition.
The idea of this POC is to create a dedicated hardware (called ARTIV1) emulating the functional architecture of V1 and hence having on one hand a huge degree of parallelism and on the other hand connections among the CPUs that reflect the non-isotropic structure of the visual cortex V1. Such a hardware that we plan to build as an integrated circuit with an industrial partner will be a veritable artificial visual cortex. It will be fully programmable and it will be able to perform many biomimetic image processing tasks that we expect to be exceptionally performant.
ARTIV1 will come to the marked accompanied by some dedicated software for image reconstruction and image recognition. However we expect that other applications will be developed by customers, as for instance softwares for optical flow estimation or for sound processing.

The ERC starting grant GECOMETHODS, on which this POC is based, tackled problems of diffusion equations via geometric control methods. One of the most striking achievements of the project has been the development of an algorithm of image reconstruction based mainly on non-isotropic diffusion. This algorithm is bio-mimetic in the sense that it replicates the way in which the primary visual cortex V1 of mammals processes the signals arriving from the eyes. It has performances that are at the state of the art in image processing. These results together with others obtained in the ERC project show that image processing algorithms based on the functional architecture of V1 can go very far. However, the exceptional performances of the primary visual cortex V1 rely not only on the particular algorithm used, but also on the fact that such algorithm “runs” on a dedicated hardware having the following features: 1. an exceptional level of parallelism; 2. connections that are well adapted to transmit information in a non-isotropic way as it is required by the algorithms of image reconstruction and recognition.
The idea of this POC is to create a dedicated hardware (called ARTIV1) emulating the functional architecture of V1 and hence having on one hand a huge degree of parallelism and on the other hand connections among the CPUs that reflect the non-isotropic structure of the visual cortex V1. Such a hardware that we plan to build as an integrated circuit with an industrial partner will be a veritable artificial visual cortex. It will be fully programmable and it will be able to perform many biomimetic image processing tasks that we expect to be exceptionally performant.
ARTIV1 will come to the marked accompanied by some dedicated software for image reconstruction and image recognition. However we expect that other applications will be developed by customers, as for instance softwares for optical flow estimation or for sound processing.

Max ERC Funding

149 937 €

Duration

Start date: 2017-04-01, End date: 2018-09-30

Project acronymAutoCode

ProjectProgramming with Big Code

Researcher (PI)Eran Yahav

Host Institution (HI)TECHNION - ISRAEL INSTITUTE OF TECHNOLOGY

Call DetailsProof of Concept (PoC), ERC-2016-PoC, ERC-2016-PoC

SummarySoftware synthesis aims to automate the creation of software by generating parts of software from a higher-level description. Until recently it was believed to be impossible to practically synthesize software beyond very small fragments. However, synthesis based on learning from existing large code-bases (“Big Code”) is making synthesis into a practical reality . The purpose of this PoC is to develop a platform that would lead to commercialization of our technology to improve programming productivity and code quality. We target two closely related applications: (1) Providing automatic assistance in programming tasks by learning from existing code, and (2) Providing on-line assessment of code quality as it is being developed using learned models. These applications have the potential to dramatically reduce time-to-market of new software, and improve its quality and security.

Software synthesis aims to automate the creation of software by generating parts of software from a higher-level description. Until recently it was believed to be impossible to practically synthesize software beyond very small fragments. However, synthesis based on learning from existing large code-bases (“Big Code”) is making synthesis into a practical reality . The purpose of this PoC is to develop a platform that would lead to commercialization of our technology to improve programming productivity and code quality. We target two closely related applications: (1) Providing automatic assistance in programming tasks by learning from existing code, and (2) Providing on-line assessment of code quality as it is being developed using learned models. These applications have the potential to dramatically reduce time-to-market of new software, and improve its quality and security.

Max ERC Funding

150 000 €

Duration

Start date: 2017-05-01, End date: 2018-10-31

Project acronymBETASCREEN

ProjectValidation of an in vivo translational medicine approach for the treatment of diabetes and diabetes complications

Researcher (PI)Yngve Per-Olof BERGGREN

Host Institution (HI)KAROLINSKA INSTITUTET

Call DetailsProof of Concept (PoC), ERC-2016-PoC, ERC-2016-PoC

SummaryValidation of an in vivo translational medicine approach for the treatment of diabetes and diabetes complications
To develop new drugs for treatment of diabetes, there is an immediate need for an in vivo approach allowing the assessment of β-cell function and survival in the living organism non-invasively, longitudinally and at single-cell resolution. We therefore transplant pancreatic islets into the anterior chamber of the eye (ACE) of mice for functional microscopic imaging. In the ACE islets become vascularized and innervated, and various aspects of β-cell function and survival can be readily imaged. Functional studies demonstrate that engrafted islets in the eye serve as representative reporters of endogenous islets in the pancreas of the same animal. We have extensively in vitro tested fluorescent biosensors that reflect key-events in β-cell function and survival. Following intraocular transplantation of human islets expressing biosensors in their β-cells into healthy or diabetic mice, they will allow non-invasive, longitudinal in vivo monitoring of 1) Ca2+ handling, 2) functional β-cell mass, 3) apoptosis and 4) proliferation. Based on the in vitro tested biosensors, the major objective is to establish a robust pharma-industry in vivo platform for validating newly developed diabetes treatment lead-compounds in early drug development. This screening service shall be performed on a commercial basis. The milestone of this proposal, to be achieved within 18 months, is the validation of the in vivo platform for testing the effects of new potential diabetes medicines on human β-cell function and survival in normal and diabetic mice.

Validation of an in vivo translational medicine approach for the treatment of diabetes and diabetes complications
To develop new drugs for treatment of diabetes, there is an immediate need for an in vivo approach allowing the assessment of β-cell function and survival in the living organism non-invasively, longitudinally and at single-cell resolution. We therefore transplant pancreatic islets into the anterior chamber of the eye (ACE) of mice for functional microscopic imaging. In the ACE islets become vascularized and innervated, and various aspects of β-cell function and survival can be readily imaged. Functional studies demonstrate that engrafted islets in the eye serve as representative reporters of endogenous islets in the pancreas of the same animal. We have extensively in vitro tested fluorescent biosensors that reflect key-events in β-cell function and survival. Following intraocular transplantation of human islets expressing biosensors in their β-cells into healthy or diabetic mice, they will allow non-invasive, longitudinal in vivo monitoring of 1) Ca2+ handling, 2) functional β-cell mass, 3) apoptosis and 4) proliferation. Based on the in vitro tested biosensors, the major objective is to establish a robust pharma-industry in vivo platform for validating newly developed diabetes treatment lead-compounds in early drug development. This screening service shall be performed on a commercial basis. The milestone of this proposal, to be achieved within 18 months, is the validation of the in vivo platform for testing the effects of new potential diabetes medicines on human β-cell function and survival in normal and diabetic mice.

Host Institution (HI)THE UNIVERSITY COURT OF THE UNIVERSITY OF ST ANDREWS

Call DetailsProof of Concept (PoC), ERC-2016-PoC, ERC-2016-PoC

SummaryBiodiversity CHANGE is a major, but still underappreciated, threat to humanity. It arises when there is unprecedented turnover in the identities of species that comprise ecological assemblages. To understand, monitor and ameliorate this CHANGE, and to enable appropriate societal responses, policy makers and conservation managers urgently need access to the best possible data. At present the ability of practitioners to elucidate ecosystem responses to anthropogenic impacts is hampered by data availability. Building on ERC AdvG BioTIME, BioCHANGE will provide a proof of concept that existing fragmented data can be assembled into an open access, authoritative database to form a crucial resource for addressing societal challenges arising from the biodiversity crisis.

Biodiversity CHANGE is a major, but still underappreciated, threat to humanity. It arises when there is unprecedented turnover in the identities of species that comprise ecological assemblages. To understand, monitor and ameliorate this CHANGE, and to enable appropriate societal responses, policy makers and conservation managers urgently need access to the best possible data. At present the ability of practitioners to elucidate ecosystem responses to anthropogenic impacts is hampered by data availability. Building on ERC AdvG BioTIME, BioCHANGE will provide a proof of concept that existing fragmented data can be assembled into an open access, authoritative database to form a crucial resource for addressing societal challenges arising from the biodiversity crisis.

Max ERC Funding

149 428 €

Duration

Start date: 2016-11-01, End date: 2018-04-30

Project acronymBiofoulRepel

ProjectBiofoulant-repelling surfaces for catheters and other biomedical devices

Researcher (PI)Jacob KLEIN

Host Institution (HI)WEIZMANN INSTITUTE OF SCIENCE

Call DetailsProof of Concept (PoC), ERC-2016-PoC, ERC-2016-PoC

SummaryThe object of this proof of concept project is to modify the surfaces of biomedical devices intended for contact with human tissue, such as catheters, stents or contact lenses, to render them repellent to biofoulants, based on discoveries made in our current ERC project HydrationLube. This will render such surfaces, and the devices, far more resistant to health-threatening infections. Our ERC project demonstrated that boundary layers based on phosphatidylcholine (PC) lipids (in the form of liposomes, bilayers or polymer-lipid complexes) can expose extremely hydrated interfaces, which are not only strongly lubricating but, as we recently showed, are also capable – particularly at hydrogel surfaces - of massively suppressing the adsorption of common biofoulants including proteins and bacteria. We now propose to use this finding to overcome, through suitable surface treatment, the undesirable effects of such fouling and biofilm formation on tissue-contacting devices, which impose a huge health and cost burden. Thus, neutralizing bacteria in biofilm may require a 1000-times higher dose of antibiotic compared to planktonic bacteria. Moreover, such infections are frequent: some 4% of all implanted vascular grafts and medical heart valves become infected, as do 2% of implanted joint prostheses and 5% of the 2x106 fracture fixation devices that are used in the U.S. alone each year. The cost of curing such infections may exceed $50,000 per case, apart from the burden of human suffering and morbidity, and they account for over 50% of all Hospital Associated Infections (HAI). The current project, working through 5 work-packages, will validate the feasibility of such anti-fouling treatments on actual devices, will carry out competitive analysis and market research, explore the commercialization process and the IPR position, and seek contacts with appropriate industrial partners to further develop the commercialization of our technology.

The object of this proof of concept project is to modify the surfaces of biomedical devices intended for contact with human tissue, such as catheters, stents or contact lenses, to render them repellent to biofoulants, based on discoveries made in our current ERC project HydrationLube. This will render such surfaces, and the devices, far more resistant to health-threatening infections. Our ERC project demonstrated that boundary layers based on phosphatidylcholine (PC) lipids (in the form of liposomes, bilayers or polymer-lipid complexes) can expose extremely hydrated interfaces, which are not only strongly lubricating but, as we recently showed, are also capable – particularly at hydrogel surfaces - of massively suppressing the adsorption of common biofoulants including proteins and bacteria. We now propose to use this finding to overcome, through suitable surface treatment, the undesirable effects of such fouling and biofilm formation on tissue-contacting devices, which impose a huge health and cost burden. Thus, neutralizing bacteria in biofilm may require a 1000-times higher dose of antibiotic compared to planktonic bacteria. Moreover, such infections are frequent: some 4% of all implanted vascular grafts and medical heart valves become infected, as do 2% of implanted joint prostheses and 5% of the 2x106 fracture fixation devices that are used in the U.S. alone each year. The cost of curing such infections may exceed $50,000 per case, apart from the burden of human suffering and morbidity, and they account for over 50% of all Hospital Associated Infections (HAI). The current project, working through 5 work-packages, will validate the feasibility of such anti-fouling treatments on actual devices, will carry out competitive analysis and market research, explore the commercialization process and the IPR position, and seek contacts with appropriate industrial partners to further develop the commercialization of our technology.

SummaryCancer heterogeneity has reinforced the need for personalized treatment modalities. Pre-therapeutic diagnostic testing of heterogeneous tumors helps avoid inefficacious treatments, optimizes targeted therapy and improves quality of life. Within targeted therapy, immunotherapy has led to significant improvements in treatment outcomes and is swiftly being integrated in diagnostic workflows. In this context, routine diagnostic tests currently do not exist, and treatments are further challenged by heterogeneity. Spatially resolved molecular probing of tumors prior to treatment would allow prediction of patient response to immunotherapeutics.
We have been developing methods to perform local biochemical reactions at micrometer length scales using nanoliter volumes of biochemicals. These methods are implemented using a scanning probe technology – the microfluidic probe (MFP) – with devices, platforms and assays adapted for application on biological substrates. With this, we are working towards multi-modal molecular profiling of tumors – tissue microprocessing (TMP). Thus far, we have demonstrated TMP for local DNA and mRNA analysis on live cells, for patterning cells and for micro-immunohistochemical tests on tissues.
Here, we will leverage TMP concepts to work on the initial steps in pre-commercializing the MFP for diagnostic testing in immunotherapy. Specifically, we aim to:
(1) Develop assays for morphological and molecular analyses of pancreatic tissues using the MFP.
(2) Adapt the assays developed in (1) to be compatible with workflows of state-of-the-art genome and transcriptome analysis for molecular profiling of tumors in diagnostics.
(3) validate these techniques for patient samples.
With this PoC grant, we envision to translate the MFP technology from the lab to the clinic for personalized immunotherapy.

Cancer heterogeneity has reinforced the need for personalized treatment modalities. Pre-therapeutic diagnostic testing of heterogeneous tumors helps avoid inefficacious treatments, optimizes targeted therapy and improves quality of life. Within targeted therapy, immunotherapy has led to significant improvements in treatment outcomes and is swiftly being integrated in diagnostic workflows. In this context, routine diagnostic tests currently do not exist, and treatments are further challenged by heterogeneity. Spatially resolved molecular probing of tumors prior to treatment would allow prediction of patient response to immunotherapeutics.
We have been developing methods to perform local biochemical reactions at micrometer length scales using nanoliter volumes of biochemicals. These methods are implemented using a scanning probe technology – the microfluidic probe (MFP) – with devices, platforms and assays adapted for application on biological substrates. With this, we are working towards multi-modal molecular profiling of tumors – tissue microprocessing (TMP). Thus far, we have demonstrated TMP for local DNA and mRNA analysis on live cells, for patterning cells and for micro-immunohistochemical tests on tissues.
Here, we will leverage TMP concepts to work on the initial steps in pre-commercializing the MFP for diagnostic testing in immunotherapy. Specifically, we aim to:
(1) Develop assays for morphological and molecular analyses of pancreatic tissues using the MFP.
(2) Adapt the assays developed in (1) to be compatible with workflows of state-of-the-art genome and transcriptome analysis for molecular profiling of tumors in diagnostics.
(3) validate these techniques for patient samples.
With this PoC grant, we envision to translate the MFP technology from the lab to the clinic for personalized immunotherapy.

Max ERC Funding

150 000 €

Duration

Start date: 2017-08-01, End date: 2018-07-31

Project acronymBioREAD

ProjectBioREAD; a Continuous Barrier Quality Monitoring System for Organs-on-Chip

Researcher (PI)Albert Van den Berg

Host Institution (HI)UNIVERSITEIT TWENTE

Call DetailsProof of Concept (PoC), ERC-2016-PoC, ERC-2016-PoC

SummaryOrgans-on-chip are expected to play a crucial role in the pharmaceutical industry for drug development and study of organs and diseases. We propose the development of an electrical detector that enables simple, versatile and continuous quality monitoring of these devices and is essential for commercialization. Combined with recent advances in stem cell technology, Organ-on-Chips can be used to do drug screening on an individual level. Therefore it can serve as instrument for personalized medicine, by determining the effectiveness of selected compounds, as well as possible side-effects to determine safe drug doses on a person-specific level. Moreover, Organs-on-Chip will greatly contribute to a further reduction in the need for animal testing. Besides the pharmaceutical industry, Organs-on-Chip hold great promise for the food and cosmetics industry to test the safety of products.
Organ-on-Chip systems need continuous monitoring of the quality of the cell barrier to guarantee reliable outcomes of the drug development tests. State-of-the-art methods, such as fluorescence and commercially available Trans-Endothelial Electrical Resistance (TEER) measurement apparatus are discontinuous, inaccurate and/or harmful for the cells and therefore unsuitable for pharmaceutical applications. Our innovation overcomes these disadvantages. It enables continuous quality monitoring of the barrier function of the organ, which is essential for the commercialization of Organs-on-Chip. The BIOS-Lab on Chip group holds an excellent record in high-quality TEER measurements, demonstrating direct current (DC) TEER-measurements in a gut-on-a-chip in a top-15 of most cited research papers in the journal Lab-on-Chip in 2015 and has ample experience in the development of a blood-brain barrier on chip. This proposal is part of the ERC-project Vascular Engineering on-chip using differentiated Stem Cells (VESCEL).

Organs-on-chip are expected to play a crucial role in the pharmaceutical industry for drug development and study of organs and diseases. We propose the development of an electrical detector that enables simple, versatile and continuous quality monitoring of these devices and is essential for commercialization. Combined with recent advances in stem cell technology, Organ-on-Chips can be used to do drug screening on an individual level. Therefore it can serve as instrument for personalized medicine, by determining the effectiveness of selected compounds, as well as possible side-effects to determine safe drug doses on a person-specific level. Moreover, Organs-on-Chip will greatly contribute to a further reduction in the need for animal testing. Besides the pharmaceutical industry, Organs-on-Chip hold great promise for the food and cosmetics industry to test the safety of products.
Organ-on-Chip systems need continuous monitoring of the quality of the cell barrier to guarantee reliable outcomes of the drug development tests. State-of-the-art methods, such as fluorescence and commercially available Trans-Endothelial Electrical Resistance (TEER) measurement apparatus are discontinuous, inaccurate and/or harmful for the cells and therefore unsuitable for pharmaceutical applications. Our innovation overcomes these disadvantages. It enables continuous quality monitoring of the barrier function of the organ, which is essential for the commercialization of Organs-on-Chip. The BIOS-Lab on Chip group holds an excellent record in high-quality TEER measurements, demonstrating direct current (DC) TEER-measurements in a gut-on-a-chip in a top-15 of most cited research papers in the journal Lab-on-Chip in 2015 and has ample experience in the development of a blood-brain barrier on chip. This proposal is part of the ERC-project Vascular Engineering on-chip using differentiated Stem Cells (VESCEL).